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Altered hypoxia inducible factor‐1 alpha levels correlate with major coronary vessel defects
Author(s) -
Wikenheiser Jamie,
Karunamuni Ganga,
Yang Ke,
Agani Faton,
Watanabe Michiko
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a232-c
Subject(s) - hypoxia (environmental) , coronary vessel , oxygen tension , coronary arteries , hyperoxia , hypoxia inducible factors , medicine , endocrinology , alpha (finance) , biology , chemistry , blood vessel , artery , oxygen , biochemistry , gene , lung , construct validity , nursing , organic chemistry , patient satisfaction
Previously we showed that hypoxia, as assessed by the hypoxia indicator EF5, is highest in the outflow tract (OFT) myocardium and other regions corresponding to the location of the major coronary vessels of the developing chicken heart. The EF5 positive tissues were also specifically positive for nuclear‐localized hypoxia inducible factor‐1 alpha (HIF‐1a), the oxygen‐sensitive component of the hypoxia inducible factor‐1 (HIF‐1) heterodimer. In this study we altered ambient oxygen levels (hypoxia 15%; hyperoxia 75–40%) during developmental stages (ED 4–9) critical to avian coronary vessel development in order to alter tissue hypoxia, HIF‐1a protein expression and its downstream targets. After incubation in these altered oxygen regimens, we assayed for coronary defects using anti‐alpha‐SMA immunohistology of sections transverse to the heart. The coronary arteries were particularly intensely labeled with anti‐alpha‐SMA that bound to smooth muscle cells investing these vessels. When incubated for 4.5 days under the abnormal oxygen levels, coronary arteries displayed deviations from their normal connections to the aorta. These findings indicate that developing coronary vessels may be subject to a level of regulation that is dependent on differential oxygen tension within cardiac tissues and subsequent HIF‐1 regulation of gene expression. Supported in part by NIH Grants HL65314, HL0775436, ES103507